tbuckley/cabot-search huggingface dataset:
POS1330 COMPARISON OF CLINICOPATHOLOGICAL FEATURES BETWEEN PATIENTS WITH AND WITHOUT HYPOCOMPLEMENTEMIA IN IgG4-RELATED KIDNEY DISEASE (IgG4-RKD): A MULTI-CENTER STUDY BY THE JAPANESE SOCIETY OF NEPHROLOGY IgG4-RKD WORKING GROUP
Authors: T. Saeki, T. Nagasawa, Y. Ubara, Y. Taniguchi, M. Yanagita, S. Nishi, M. Nagata, Y. Yamaguchi, T. Saito, H. Nakashima, M. Kawano
Journal: Annals of the Rheumatic Diseases (2022)

Background Although hypocomplementemia has been frequently reported in IgG4-related kidney disease (IgG4-RKD), few studies have investigated differences in the clinicopathological features of IgG4-RKD with and without hypocomplementemia in a relatively small cohort1,2). Objectives To compare the clinicopathological features of Japanese patients with and without hypocomplementemia in IgG4-RKD. Methods We retrospectively examined the clinicopathological features of 60 patients with definitively diagnosed IgG4-RKD, collected from the institutions associated with the Japan IgG4-RKD working group between December 2010 and May 2019, with reference to the presence of hypocomplementemia. Results Among the patients included, 42 (70%) had hypocomplementemia. In the latter group, serum levels of IgG and non-IgG4 IgG, calculated as total IgG minus IgG4, were significantly higher (mean IgG level, 3832 vs 2626 mg/dl, p=0.005, mean non-IgG4 IgG level, 2775 vs 1627 mg/ml, p =0.000). Renal function at diagnosis tended to be lower (mean eGFR level 42.4 vs 53.6 ml/min), although not to a significant degree (p=0.07). There were no significant inter-group differences in the levels of serum IgG4 and IgE, or in the number of extra-renal involved organs. Renal pathology specimens were obtained from 53 patients, 70% of whom had hypocomplementemia. In the hypocomplementemia group, light microscopy demonstrated a significantly broader extent of interstitial inflammatory cell infiltration (p=0.035), and immunofluorescence revealed a higher frequency of IgG or complement deposition on the renal tubular basement membrane (TBM) (p=0.048). C1q deposition on the TBM was evident only in the hypocomplementemia group. There was no significant inter-group difference in the presence of storiform fibrosis, the degree of interstitial fibrosis, the number of infiltrating IgG4-positive cells, or the frequency of membranous glomerulonephritis. Conclusion Hypocomplementemia in IgG4-RKD is associated with elevated levels of IgG subclasses other than IgG4, and may be related to progression of renal inflammation. References [1]Wang R, et al. Role of complement system in patients with biopsy-proven immunoglobulin G4-related kidney disease. Hum Pathol. 2018;81:220-228. [2]Fujisawa Y, et al. Hypocomplementemia is related to elevated serum levels of IgG subclasses other than IgG4 in IgG4-related kidney disease. Mod Rheumatol. 2021;31(1):241-248. Disclosure of Interests None declared
AB0920 Safety of Apremilast in PsA patients with history of malignancies or active cancer: a retrospective study
Authors: D. V. A. Sabella, V. Venerito, M. Fornaro, F. Cacciapaglia, M. G. Anelli, F. Arezzo, V. Internò, G. Lopalco, F. Iannone
Journal: Annals of the Rheumatic Diseases (2022)

Background One of the most intriguing aspects in the management of patients with inflammatory arthritis is the safety of novel therapies in those with a recent history of malignancy or active neoplasm. In this regard, apremilast (APR), an oral PDE4 inhibitor, is emerging as one of the safest therapeutic options in patients with PsA with comorbid cancer. Objectives This retrospective study aims to assess the effectiveness and safety of APR in PsA patients with a recent history of malignancy or active cancer. Methods We retrospectively observed patients with a history of neoplasm diagnosed from 1997 to 2021, who underwent apremilast treatment from 2017 to 2021 in a tertiary care centre. We recorded demographic and clinical characteristics at APR baseline and last visit. Furthermore, we recorded the eventual recurrence of primary cancer or the onset of new neoplasms. Paired t-test was used to assess the difference of continuous variables at different follow-ups. Results Thirteen patients (sex: female 6/13, 46,15%; mean age (mean ± 63,7 years sd ± 9,9 years)) started Apremilast between 2017 to 2021 in a tertiary care center. We assessed their clinical condition using DAPSA, LEI and PASI score in the baseline and in the last visit. Mean follow-up time was 32,02 ± 18,92 months. Mean DAPSA at baseline 20,55 ± 9,15 decreased to 16,21 ± 1,73 at last visit. Similarly mean LEI at baseline was 1,23 ± 1,58 and decreased to 0,61 ± 0,35 at last visit, even in absence of statistical significance (p=0,15). Conversely mean PASI at baseline (1,76 ± 2,57) did not show a decrease (1,61 ± 0,93); Ten patients were still treated with apremilast at last available follow-up. Patient 6 (Table 1) experienced the relapse of Ductal Breast Papilloma. For patient 8, a relapse of primary cancer occurred. Patient 9 had the onset of a new neoplasm. The APR was not discontinued as such malignancies were not considered as treatment associated. Three patients (4, 6, 10) discontinued APR due to intolerance or lack of efficacy. Conclusion APR seems a safe option in PsA patients with a recent history of malignancy or active cancer, improving articular involvement. Disclosure of Interests None declared
AB1144 COGNITIVE AND PSYCHOSOCIAL OUTCOME IN CHILDREN WITH MULTISYSTEM INFLAMMATORY SYNDROME FOLLOWING SARS-CoV-2 INFECTION
Authors: D. Gosar, M. Zajc Avramovič, N. Emersic, M. Šušterič, M. M. Šömen, D. Osredkar, T. Avcin
Journal: Annals of the Rheumatic Diseases (2022)

Background Despite the low rate of neurological deficits following the SARS-COV-2 infection in the pediatric population, children and adolescents who develop multisystem inflammatory syndrome (MIS-C) after being infected with SARS-COV-2 are at a higher risk for neurological abnormalities and brain injury, increasing the risk of adverse cognitive and psychiatric outcome. Objectives Given the increased risk of central nervous system impairment we chose to conduct a prospective study looking at the cognitive and psychosocial outcome of patients with MIS-C. Methods Our study included 27 of the 29 patients between 2 to 18 years of age (M = 11.1, SD = 4.4) who were treated for MIS-C from the onset of the SARS-COV-2 pandemic until the beginning of May 2021 at the only tertiary care pediatric immunology center in Slovenia. We assessed these patients 6 months after diagnosis using the age-appropriate Wechsler intelligence scales and a battery of neuropsychological test measuring attention, executive function, memory and fine motor skills. We also asked parents to report on patients’ psychosocial outcome using the Achenbach Child Behavior Checklist. Results By using Bayesian statistics to take into account parental education and any potential pre-morbid learning difficulties we found no evidence of impairment on measures of intelligence. However, the posterior distribution of scores on neuropsychological measures indicated that a significant proportion of patients scored 1SD bellow expected levels on measures of attention (31%), executive function (28%) and visual memory (35%). Increased symptoms of depression, anxiety and attention difficulties were also reported by parents, although their extent did not rise to a clinically significant level. Conclusion The findings from our cohort suggest that the cognitive and psychosocial outcome of patients with MIS-C is generally favorable, although up to 35% may experience specific neuropsychological deficits more than 6 months after diagnosis. The most commonly impaired cognitive domains seem to be attention, executive function and visual memory. Acknowledgements Funding for this work was provided by the Slovenian Research Agency grant J3-3061 and University Medical Centre grant 20210069. Support was also provided by Dušica Boben and the publisher Center za psihodiagnostična sredstva by providing the local adaptations of psychological assessment tools. Disclosure of Interests David Gosar Speakers bureau: Biogen, Novartis, Mojca Zajc Avramovič: None declared, Nina Emersic: None declared, Mateja Šušterič: None declared, Maja Maša Šömen: None declared, Damjan Osredkar: None declared, Tadej Avcin: None declared
AB1106 HOW HAS THE COVID-19 PANDEMIC AFFECTED OUR RHEUMATOLOGY PATIENTS USING BIOLOGICAL/TARGETED DMARDS?
Authors: S. Gulle, Y. Erez, A. Karakas, T. Yüce İnel, S. B. Kocaer, T. Demirci Yildirim, G. Can, İ. Sari, M. Birlik, F. Onen
Journal: Annals of the Rheumatic Diseases (2022)

Background Bioinformatics data, which are becoming more detailed day by day, show that male gender, advanced age, smoking, and comorbidities are associated with poor outcome of COVID-19. However, it is well known that the active disease state that may occur as a result of discontinuing the drugs also increases the susceptibility to infection. Objectives It was aimed to investigate the effects of the COVID-19 pandemic on the course and treatment of rheumatic disease in patients with inflammatory rheumatic musculoskeletal disease (iRMD) using biological or targeted synthetic DMARDs (b/tsDMARDs). Methods The study was carried out in two stages: while investigating the delay of b/tsDMARD treatment in the first 3 months of the pandemic with the fear of infected by SARS-Cov-2 in the first stage, in the second stage, it was investigated whether all patients who decided to continue treatment after interruption in the 12-month period. Results A total of 521 patients were included in the study. It was seen that the iRMD diagnosis were listed as SpA (54.3%), RA (25.7%), PsA (8.4%), vasculitis (6.1%), and others (5.4%). The overall 12-month drug retention rate was 92.3%. Concurrent use of hydroxychloroquine (HCQ) (HR=1.49), iv bDMARD use (HR=1.34), and a history of discontinuation of drug in the first 3 months of the pandemic (HR=1.19) were determined as factors that reduced 12-month drug retention rates. During a total of 12 months, 34 (6.5%) of patients had COVID-19. COVID-19 was severe in 7 patients and 5 of these patients died.The use of GC (HR=3.81) and having a diagnosis of ILD/COPD (HR=4.96) were found to increase the risk of infected by SARS-CoV-2. Table 1. Comparison of demographic and clinical characteristics of patients with COVID-19 Demographics COVID-19 (-) (n=487 ) COVID-19 (+) (n=34 ) P Median (Min./Max. ) Median (Min./Max. ) Age 48 (18-86) 48 (18-82) 0.615 Disease Duration 130 (22-478) 144 (48-519) 0.573 b/ts DMARD Duration 45 (12-192) 26 (14-170) 0.253 GC dose, mg 4 (1-16) 4 (2-16) 0.863 n (% ) n (% ) Gender, F 259 19 0.909 COVID-19 diagnosis and outcome Hospitalization ─ 11 (32.3 ) ─ Mortality ─ 5 (14.7 ) ─ Active disease (anytime during the pandemic ) 82 (16.4) 9 (26.5) 0.246 ILD and/or COPD 14 (2.9) 4 (8.9 ) 0.002 n (% ) n (% ) b/tsDMARD type 0.049 TNFi 382 (78.4 ) 15 (44.1) 0.243 Tocilizumab 19 (3.9) 2 (5.9) 0.684 Abatacept 13 (2.7) 1 (2.9) 0.886 Rituximab 9 (1.8) 6 (17.6 ) 0.001 GC 83 (17.0) 17 (50.1 ) 0.001 Conclusion The results of this study with a long follow-up period suggest that the retention rates of b/tsDMARD treatment increased with good communication with iRMD patients during the COVID-19 pandemic. References [1]Favalli EG, et al. (2020) Arthritis Rheumatol 72:1600–1606. [2]Landewé RB, et al. Ann Rheum Dis 79:851–858. Disclosure of Interests None declared
AB0291 COMORBIDITIES PROFILES IN SEROPOSITIVE RHEUMATOID ARTHRITIS VERSUS SERONEGATIVE RHEUMATOID ARTHRITIS
Authors: E. Hannech, A. Ben Tekaya, O. Saidane, S. Bouden, R. Leila, R. Tekaya, I. Mahmoud, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2022)

Background Patients with seropositive rheumatoid arthritis (RA) (positive Rheumatoid Factor (RF)) are more susceptible to extra-articular manifestations [1]. The role of RF in the occurrence of comorbidity is not clear. Objectives We aimed to compare comorbidities among patients with seropositive RA versus patients with seronegative RA. Methods We conducted a retrospective study in our rheumatology department including 255 patients with established RA according to the ACR/EULAR 2010 criteria. Patients were divided in two groups according to their Rheumatoid Factor (RF) profile: seropositive RA (positive RF), seronegative RA (negative RF). Comorbidities were investigated and compared between the two patients groups. Results There were 206 seropositive RA and 49 seronegative RA. Gender distribution was similar in the two groups: 82% female and 18% male in seropositive RA; 85% female and 15% male in seronegative RA (p=0.5). Smoking was noted in 15% patients with seropositive RA and in 11% patients with seronegative RA without any difference (p=0.5). Comorbidities were noted in 49% of seropositive RA and in 45% of seronegative RA without any significant difference (p=0.6). Obesity (BMI ≥ 30kg/m 2 ) was noted in 31% of seropositive RA and in 36% of seronegative RA (p=0.7). Diabetes was noted in 18 % seropositive RA and in 26% seronegative RA patients (p=0.1). Hypertension was noted in 31% seropositive RA patients and in 30% seronegative RA (p=0.8). Heart disease was present in 6% seropositive RA and in 7% seronegative RA (p=0.9). Dyslipidemia was noted in 40% seropositive RA and in 20% seronegative RA (p=0.1). Gastrointestinal comorbidities were observed in only seropositive RA patients (11%). Respiratory comorbidities were noted in 27% seropositive RA and in 28% seronegative RA without any significant difference (p=0.6). Regarding mental health problems, depression was noted in 7% seropositive RA and in 14% seronegative RA without any significant difference (p=0.4). Conclusion Our study showed that comorbidities were comparable in seropositive and seronegative RA. It seems that RF does not influence the prevalence of comorbidities in RA patients. References [1]Sahatçiu-Meka V, Rexhepi S, Manxhuka-Kërliu S, Rexhepi M. Extra-Articular Manifestations of Seronegative and Seropositive Rheumatoid Arthritis. Bosn J Basic Med Sci . 2010;10(1):26–31. Disclosure of Interests None declared
AB0490 INFLAMMATORY MUSCULOSKELETAL ABNORMALITIES BY CONTRAST ENHANCED MRI SHOW A SPECIFIC PROFILE IN SLE PATIENTS
Authors: P. Corzo Garcia, A. Agustí Claramunt, I. Garcia-Duitama, I. Carrión Barberà, S. Marsico, J. Monfort, T. C. Salman Monte
Journal: Annals of the Rheumatic Diseases (2022)

Background Joint involvement in SLE is the most frequent manifestation and often it is the first clinical symptom. Despite this, it is not well characterised and demographic, serological and clinicotherapeutic correlations have not been well stablished 1 . Objectives We aim to determinate if there is a demographic, clinic or serological profile related to inflammatory joint involvement of hand and/or wrist (sinovitis, bone marrow edema, erosions, tenosynovitis or peritendonitis) confirmed by contrasted MRI in SLE patients. Methods Consecutive SLE patients fulfilling SLICC criteria both symptomatic and asymptomatic for joint involvement were recruited. Contrasted MRI of non-dominant hand/wrist was performed for joint and tendon evaluation. Sociodemographic, clinicotherapeutic and serological data were collected and statistically analysed along with each MRI abnormality. Results 83 subjects were recruited. Erosions and synovitis were more frequent at advanced age (55±12.61 vs 45.06±12.18 years, p 0.001 and 52.78±12.99 vs 44.95±12.49 years, p 0.011). Synovitis is less frequent in patients with renal involvement (6.7% vs 24.3%, p 0.031). No other SLE organ-specific involvement showed statistical correlation. Neither SLE related autoantibodies (ANA, DNAds, Sm, RNP, Ro, La, antiphospholipid), complement fractions, ESR nor CRP correlated with MRI lesions, except for erosions which showed lower DNAds titers (15.94±49.56 vs. 27.23±62.41, p 0.008). Patients with bone marrow edema received more methotrexate (25% vs 6.3%, p 0.033), and those with erosions and peritendonitis received less mycophenolate (5.6% vs 22.9%, p 0.034; y 0% vs 12.8%, p 0.026). Peritendonitis was the only alteration related to higher SLEDAI (7±2.45 vs 3.64±3.34, p 0.018). None of the musculoskeletal abnormalities correlated with accrual damage. Conclusion SLE patients with joint and/or tendon abnormalities confirmed by MRI are usually older and have less renal involvement, receiving more methotrexate and less mycophenolate than those who do not show musculoskeletal involvement. References [1]Ceccarelli F et al. Joint involvement in systemic lupus erythematosus: From pathogenesis to clinical assessment. Semin Arthritis Rheum. 2017;47:53-64 Acknowledgements GSK and Societat Catalana de Reumatologia granted this work, we want to acknowledge them for their collaboration Disclosure of Interests PATRICIA CORZO GARCIA Grant/research support from: GSK, Anna Agustí Claramunt: None declared, Ivan Garcia-Duitama: None declared, Irene Carrión Barberà: None declared, Salvatore Marsico: None declared, Jordi Monfort Grant/research support from: GSK, Tarek Carlos Salman Monte Grant/research support from: GSK
Neofunctionalization of a Noncoding Portion of a DNA Transposon in the Coding Region of the Chimerical Sex-Determining Gene <i>dm-W</i> in <i>Xenopus</i> Frogs
Authors: Shun Hayashi, Kosuke Suda, Fuga Fujimura, Makoto Fujikawa, Kei Tamura, Daisuke Tsukamoto, Ben J Evans, Nobuhiko Takamatsu, Michihiko Ito
Journal: Molecular Biology and Evolution (2022)

Abstract Most vertebrate sex-determining genes (SDGs) emerge as neofunctionalized genes through duplication and/or mutation of ancestral genes that are involved with sexual differentiation. We previously demonstrated dm-W to be the SDG in the African clawed frog Xenopus laevis and found that a portion of this gene emerged from the masculinization gene dmrt1 after allotetraploidization by interspecific hybridization between two ancestral species around 17–18 Ma. dm-W has four exons consisting of a noncoding exon 1, dmrt1-derived exons 2 and 3, and an orphan exon 4 (Ex4) of unknown origin that includes coding sequence (CDS). In this study, we searched for the origin of Ex4 and investigated the function of the CDS of this exon. We found that the Ex4-CDS is derived from a noncoding portion of the hAT-10 family of DNA transposon. Evolutionary analysis of transposons and determination of the Ex4 sequences from three other species indicated that Ex4 was generated before the diversification of most or all extant allotetraploid species in subgenus Xenopus, during which time we hypothesize that transposase activity of this hAT superfamily was active. Using DNA–protein binding and transfection assays, we further demonstrate that the Ex4-encoded amino acid sequence increases the DNA-binding ability and transrepression activity of DM-W. These findings suggest that the conversion of the noncoding transposon sequence to the CDS of dm-W contributed to neofunctionalization of a new chimeric SDG in the ancestor of the allotetraploid Xenopus species, offering new insights into de novo origin and functional evolution of chimerical genes.
AB1504 WILL YOU CHOOSE RHEUMATOLOGY? SURVEY ON THE ATTRACTIVENESS OF RHEUMATOLOGY AMONG MOROCCAN STUDENTS, INTERNS AND FRESHLY GRADUATED DOCTORS.
Authors: A. Anass, T. Fatima Zahrae, H. Fouzia, B. Khadija, F. Abourazzak
Journal: Annals of the Rheumatic Diseases (2022)

Background In several countries, studies have shown that fewer medical students choose rheumatology as specialty. In Morocco no study has yet focused on this subject. Objectives The aim of our study is to assess the attractiveness of rheumatology as a specialty among Moroccan medical students, recently graduates and interns, and to analyze the factors that may be associated with it. Methods An online survey was sent to 297 medical students who had started their hospital practice, to 100 medical interns (students in 6th and 7th year who successfully passed the internship competition) and to 280 freshly graduated doctors (residency program candidates before choosing a medical or surgical specialty). The survey covered three areas: anonymous social and demographic informations, data on clinical trainee in a rheumatology department, and the attitude toward rheumatology as a specialty. Descriptive data were collected and Chi 2 Tests were used to assess differences between groups, Logistic regression was performed to investigate associations between demographic and exposure variables and the choice of rheumatology as a career. Results We collected responses from 161 students (response rate: 54%), 68 interns (68%) and 89 freshly graduated doctors (32%). The demographic characteristics are presented in Table 1. Table 1. Medical students (N=161) Interns (N=68) Freshly graduated doctors (N=89) Age * 21.5 ±1 24.2 ±1.1 28.62.3 Gender (females) (%) + 93 (57.8) 30 (44.1) 64 (71.9) level (%) + Third year: 44 (27.3) First year: 44 (64.7) - Fourth year: 53 (32.9) Second year: 24 Fifth year:64 (39.8) (35.3) Training in a rheumatology departement (%) + 118 (73.3) 28 (41.2) 37 (41.6) Dduration of training (weeks) * 3.4 ± 0.7 5.3 ±1.4 6.3 ±2.6 (*) expressed as a number and percentage /(+) expressed as a mean and standard deviation 73% of students, 41.2% of interns and 41.6% of graduates said they had already completed a clinical trainee in a rheumatology department. While 41.6% of students and 43.8% of graduates consider the possibility of choosing rheumatology as their specialty, only 11.2% of students, 5.9% of interns and 7.9% of graduates said that rheumatology is their dream career specialty. In uni and multivariate analysis, clinical exposure to rheumatology is retained as the main statistically significant factor predicting the choice of rheumatology in all categories (Odds ratio (95% CI) = 0.191 (0.07- 0.497; p= 0.02)), to this is added the female sex among freshly graduated doctors (Odds ratio (95% CI) = 4.02 (1.251- 12.918; p= 0.001). Conclusion Our study showed that rheumatology is considered a fascinating specialty by Moroccan medical students and freshly graduated doctors. Clinical exposure to rheumatology is the strongest predictor factor for choosing rheumatology as a future career. Disclosure of Interests None declared